The present invention relates to a series of new piperazinylquinazoline and homopiperazinylquinazoline derivatives which have valuable antihypertensive activity, to methods for the preparation of such compounds and to their use.
A variety of quinazoline derivatives, including some piperazinyl- and homopiperazinyl-quinazoline derivatives, are known and many of these are known to have hypotensive (or antihypertensive) activity. For example, U.S. Pat. No. 3,511,836 discloses as having valuable hypotensive properties a very considerable number of quinazoline derivatives, including some which may be represented by the formula: ##STR2## in which:
R.sup.a and R.sup.b each represent hydrogen atoms or C.sub.1 -C.sub.3 alkoxy groups, at least one of them being an alkoxy group,
R.sup.c and R.sup.d each represent hydrogen atoms, alkyl groups, alkenyl groups, hydroxyalkyl groups, phenyl groups, benzyl groups, phenethyl groups, furfuryl groups or cycloalkyl groups, and
Z represents, amongst many other alternatives, an alkanoyl group, a benzoyl group or a 3,4,5-trimethoxybenzoyl group.
U.S. Pat. No. 4,060,615 also discloses a variety of piperazinylquinazoline derivatives, which may be represented by the general formula: ##STR3## in which:
R.sup.e represents an amino or hydrazino group; and
R.sup.f represents a cycloalkyl, methylcycloalkyl or cycloalkenyl group.
U.S. Pat. No. 3,920,636 discloses a series of 4-amino-2-(4-substituted homopiperazinyl-6,7-dimethoxyquinazoline derivatives and suggests that they may be used as hypotensive agents.
In practice, however, only one of these known quinazoline derivatives has actually been used. This compound, which is one of the compounds disclosed in U.S. Pat. No. 3,511,836 is known by the name prazosin and has the formula: ##STR4##
Although prazosin has very useful antihypertensive activity, its maximum hypotensive effect tends to be achieved very quickly and the effect tends also to diappear quickly: the very rapid hypotensive effect of prazosin can cause problems and its rapid disappearance means that the compound must be administered frequently. There is, therefore, a need for compounds which develop their antihypertensive activity more slowly and where the antihypertensive effect is prolonged. Moreover, of course, there is a need for compounds having better antihypertensive activity than prazosin.